Health Effects of Substituting Sugary Beverages With Artificially-sweetened Beverages or Water (SUB-POP)

SUBstituting With Preferred Options: Health Effects of Substituting Sugar-sweetened Beverages With Non-caloric Beverages in Adults With Overweight and Obesity

Sugar-sweetened beverages (SSBs) contribute an alarming ~7% of calories in the US diet among adults, making SSBs the single largest source of added sugar. However, whether artificially sweetened beverages are a healthful alternative for reducing SSB intake among habitual SSB consumers is unknown. Therefore, the investigators will conduct a 4-arm randomized diet intervention trial to test the effects of substituting SSBs with calorie-free alternatives on body weight and health, among habitual SSB consumers with overweight/obesity.

Study Overview

• Status: Active, not recruiting
• Conditions: Body Weight
• Intervention / Treatment: Behavioral: Maintain usual SSBs; Behavioral: Study app; Behavioral: Beverage delivery; Behavioral: Substitute to non-SSBs

Detailed Description

The SUBstituting with Preferred OPtions (SUB-POP) trial, is a parallel-arm randomized controlled trial (RCT) to test the effects of substituting SSBs with non-caloric options on body weight and markers of type 2 diabetes and cardiometabolic health. Eligible adult participants will be randomized to 1 of 4 beverage groups and receive at-home monthly deliveries of beverages for 6 months. In-person clinic visits will be conducted at baseline, 6, and 12 months. After the 6 months of assigned beverage substitution and delivery, all participants will be instructed to substitute SSBs with water only for a final 6-month observational period. In-person clinic visits will collect technician-measured anthropometrics, blood pressure, biospecimen samples (blood, urine, stool [subset]), and assess physical activity, diet, beverage frequency, and taste preference. The SUB-POP app-based assessments and online diet recall will ascertain daily beverage intake, while diet (via 3 24-hour recalls), physical activity, and overall beverage frequency will be collected every 1-3 months. A subset will receive at-home digital scales to transmit daily body weight for energy balance and caloric compensation modeling. SUB-POP is a novel RCT that will enroll adult regular SSB consumers with overweight or obesity to evaluate the effectiveness of substituting SSBs with non-caloric options in a real-world, un-blinded setting. The trial will leverage social media recruitment methods, achieve ≥30% non-White participants, implement innovative intervention delivery, adherence, and data collection tools, and partition the artificially-sweetened beverage (ASB) substitution intervention to the two most common artificial sweetener types (aspartame, sucralose) to explore potential heterogeneity. Whether ASBs, which are largely free of calories and sugar, provide a healthful interim strategy to transition to water among habitual SSB consumers is unknown. Thus, by addressing this large gap in the understanding of how to address a highly prevalent and concerning dietary exposure, the investigators will inform dietary guidelines and clinical recommendations for the prevention of obesity, type 2 diabetes, and cardiometabolic disease risks. The primary outcomes are change in body weight from baseline to 6 months between the 3 beverage substitution groups (aspartame ASBs, sucralose ASBs, and water) vs. the maintain SSBs control group, adjusting for multiple comparisons. The investigators and staff will be blinded to group assignment at outcome assessments. Intention-to-treat analysis will be used.

After 9/1/2023 the 2 ASB intervention groups (sucralose, aspartame) are combined into a single ASB intervention group; participants randomized on or after 9/1/2023 will be randomized to 1 of 3 beverage groups: maintain SSBs (months 0-6; then switch to water months 6-12); switch to ASBs (months 0-6; then switch to water months 6-12); switch to water (months 0-12). The primary outcomes are change in body weight from baseline to 6 months between the 2 beverage substitution groups (ASBs [all ASB intervention groups combined] and water) vs. the maintain SSBs control group, adjusting for multiple comparisons.

• Study Type: Interventional
• Enrollment (Estimated): 460
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Adults aged 20-69 years
2. Consume ≥1 serving/day (12 oz.) of SSBs (SSBs include soda, fruit drinks, energy drinks, sports drinks, and sweetened waters, sweetened with high fructose corn syrup, sucrose, or fruit juices. SSBs do not include 100% fruit juice, sweetened teas, or flavored milk.)
3. BMI 25.0 to 45.0 kg/m2
4. Access to a smartphone and willingness and ability to download study app
5. Willing to consume beverages consistent with any of the 4 possible group assignments for 6 months

Exclusion Criteria:

1. Physician diagnosis of T2D or fasting glucose ≥126 mg/dL at in-person screening visit
2. Intention to move away from greater Boston area within 1 year from randomization
3. Major medical illness (known cardiovascular disease, cancer, kidney disease, cirrhosis, etc.)
4. Phenylketonuria (PKU)
5. Medication that may affect weight or other study endpoints
6. Another family or household member participating in the study
7. Pregnant in the past 12 months, currently breastfeeding, or planning to become pregnant during the study period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Maintain SSBs (Control); Instruction to maintain baseline intake of SSBs (months 0-6); then switch to water only (months 6-12)	Behavioral: Maintain usual SSBs; Instruction/guidelines to maintain baseline intake of SSBs (months 0-6); then switch to water only (months 6-12); Behavioral: Study app; Engage with a motivational mobile app to track beverage intake and complete study data collection; Behavioral: Beverage delivery; Select from approved beverages for a monthly at-home delivery (months 0-6)
Experimental: Substitute Aspartame ASBs (participants randomized through 8/31/2023); Instruction/guidelines to eliminate SSBs and replace, where possible with beverages artificially sweetened with aspartame (months 0-6); then switch to water only (months 6-12)	Behavioral: Study app; Engage with a motivational mobile app to track beverage intake and complete study data collection; Behavioral: Beverage delivery; Select from approved beverages for a monthly at-home delivery (months 0-6); Behavioral: Substitute to non-SSBs; Instruction/guidelines to eliminate SSBs and replace, where possible, with beverages consistent to group assignment (months 0-6); then switch to water only (months 6-12)
Experimental: Substitute Sucralose ASBs (participants randomized through 8/31/2023); Instruction/guidelines to eliminate SSBs and replace, where possible with beverages artificially sweetened with sucralose (months 0-6); then switch to water only (months 6-12)	Behavioral: Study app; Engage with a motivational mobile app to track beverage intake and complete study data collection; Behavioral: Beverage delivery; Select from approved beverages for a monthly at-home delivery (months 0-6); Behavioral: Substitute to non-SSBs; Instruction/guidelines to eliminate SSBs and replace, where possible, with beverages consistent to group assignment (months 0-6); then switch to water only (months 6-12)
Experimental: Substitute Water; Instruction/guidelines to eliminate SSBs and replace with water (months 0-12)	Behavioral: Study app; Engage with a motivational mobile app to track beverage intake and complete study data collection; Behavioral: Beverage delivery; Select from approved beverages for a monthly at-home delivery (months 0-6); Behavioral: Substitute to non-SSBs; Instruction/guidelines to eliminate SSBs and replace, where possible, with beverages consistent to group assignment (months 0-6); then switch to water only (months 6-12)
Experimental: Substitute ASBs (participants randomized on or after 9/1/2023); Instruction/guidelines to eliminate SSBs and replace, where possible with beverages artificially sweetened with choice of non-nutritive sweeteners such as sucralose or aspartame	Behavioral: Study app; Engage with a motivational mobile app to track beverage intake and complete study data collection; Behavioral: Beverage delivery; Select from approved beverages for a monthly at-home delivery (months 0-6); Behavioral: Substitute to non-SSBs; Instruction/guidelines to eliminate SSBs and replace, where possible, with beverages consistent to group assignment (months 0-6); then switch to water only (months 6-12)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Change at 6 months	Change in total body weight calculated as the month 6 weight minus the baseline weight	Baseline, Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Waist Circumference Change	Calculated as month 6 minus baseline value	Baseline, Month 6
Sussex Sweet Taste Preference Score Change (0 to 100 where higher score indicates greater liking of sweet taste)	Calculated as month 6 minus baseline value	Baseline, Month 6
Beverage Intake Change (oz/d)	Calculated as month 6 minus baseline value	Baseline, Month 6
Fasting Plasma Glucose Change	Calculated as month 6 minus baseline value	Baseline, Month 6
Fasting Blood Insulin Change	Calculated as month 6 minus baseline value	Baseline, Month 6
HOMA-IR Change	Calculated as month 6 minus baseline value	Baseline, Month 6
HbA1c Change	Calculated as month 6 minus baseline value	Baseline, Month 6
TG/HDL Ratio Change	Calculated as month 6 minus baseline value	Baseline, Month 6
Weight Change Sustainability	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Waist Circumference Change	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Sussex Sweet Taste Preference Score Change (0 to 100 where higher score indicates greater liking of sweet taste)	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Total Beverage Intake Change (oz/d)	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
SSB Beverage Intake Change (oz/d)	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
ASB Beverage Intake Change (oz/d)	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Water Intake Change (oz/d)	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
HOMA-IR Change	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Fasting Blood Insulin Change	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Fasting Plasma Glucose Change	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
HbA1c Change	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Triglycerides Change	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
TG/HDL Change	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
HDL-C Change	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
LDL-C Change	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Blood Pressure (Systolic and Diastolic) Change	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
hsCRP Change	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Interleukin-6 Change	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Alternative Healthy Eating Index 2015 Diet Score Change (Scale 0 to 100 with higher score indicating greater adherence to the dietary pattern)	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Self-Reported Added Sugar Change (g/d from 24 hour diet recall)	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Self Reported Added Sugar Change (%kcal/d from 24 hour diet recall)	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Sweets/Desserts Change (serv/d from 24 hour diet recall)	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Total Physical Activity Change (MET-hrs/wk)	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12
Energy Compensation (kcal/d) Estimated from Repeated Body Weights (Assessed via At-Home Scale) vs. Repeated Energy Intake (Derived from Repeated Self-Reported 24-Hour Diet Recalls)	Calculated as month 6 minus baseline value, month 12 minus month 6 value	Baseline, Month 6, Month 12

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Deirdre Tobias, ScD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2021
• Primary Completion (Estimated): May 21, 2026
• Study Completion (Estimated): May 21, 2026

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Prevention; Artificial sweeteners; Weight control; Water; Sugar-sweetened beverages; Beverages
• Additional Relevant MeSH Terms: Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Body Weight; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Benzocaine
• Other Study ID Numbers: 2020p002494; 1R01DK125803-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No